PURPOSE: Pearson syndrome is a very rare metabolic disorder that is usually present in infancy with transfusion dependent macrocytic anemia and multiorgan involvement including exocrine pancreas, liver and renal tubular defects. The disease is secondary to a mitochondrial DNA deletion that is variable in size and location. Endocrine abnormalities can develop, but are usually not part of the initial presentation. We report two patients who presented with unusual endocrine manifestations, neonatal diabetes and adrenal insufficiency, who were both later diagnosed with Pearson syndrome. METHODS: Medical records were reviewed. Confirmatory testing included: mitochondrial DNA deletion testing and sequencing of the breakpoints, muscle biopsy, and bone marrow studies. RESULTS: Case 1 presented with hyperglycemia requiring insulin at birth. She had several episodes of ketoacidosis triggered by stress and labile blood glucose control. Workup for genetic causes of neonatal diabetes was negative. She had transfusion dependent anemia and died at 24 months due to multisystem organ failure. Case 2 presented with adrenal insufficiency and anemia during inturcurrent illness, requiring steroid replacement since 37 months of age. He is currently 4 years old and has mild anemia. Mitochondrial DNA studies confirmed a 4.9 kb deletion in patient 1 and a 5.1 kb deletion in patient 2. CONCLUSION: The patients reported highlight the importance of considering mitochondrial DNA disorders in patients with early onset endocrine dysfunction, and expand the knowledge about this rare mitochondrial disease.
PURPOSE:Pearson syndrome is a very rare metabolic disorder that is usually present in infancy with transfusion dependent macrocytic anemia and multiorgan involvement including exocrine pancreas, liver and renal tubular defects. The disease is secondary to a mitochondrial DNA deletion that is variable in size and location. Endocrine abnormalities can develop, but are usually not part of the initial presentation. We report two patients who presented with unusual endocrine manifestations, neonatal diabetes and adrenal insufficiency, who were both later diagnosed with Pearson syndrome. METHODS: Medical records were reviewed. Confirmatory testing included: mitochondrial DNA deletion testing and sequencing of the breakpoints, muscle biopsy, and bone marrow studies. RESULTS: Case 1 presented with hyperglycemia requiring insulin at birth. She had several episodes of ketoacidosis triggered by stress and labile blood glucose control. Workup for genetic causes of neonatal diabetes was negative. She had transfusion dependent anemia and died at 24 months due to multisystem organ failure. Case 2 presented with adrenal insufficiency and anemia during inturcurrent illness, requiring steroid replacement since 37 months of age. He is currently 4 years old and has mild anemia. Mitochondrial DNA studies confirmed a 4.9 kb deletion in patient 1 and a 5.1 kb deletion in patient 2. CONCLUSION: The patients reported highlight the importance of considering mitochondrial DNA disorders in patients with early onset endocrine dysfunction, and expand the knowledge about this rare mitochondrial disease.
Authors: Sumit Parikh; Amy Goldstein; Amel Karaa; Mary Kay Koenig; Irina Anselm; Catherine Brunel-Guitton; John Christodoulou; Bruce H Cohen; David Dimmock; Gregory M Enns; Marni J Falk; Annette Feigenbaum; Richard E Frye; Jaya Ganesh; David Griesemer; Richard Haas; Rita Horvath; Mark Korson; Michael C Kruer; Michelangelo Mancuso; Shana McCormack; Marie Josee Raboisson; Tyler Reimschisel; Ramona Salvarinova; Russell P Saneto; Fernando Scaglia; John Shoffner; Peter W Stacpoole; Carolyn M Sue; Mark Tarnopolsky; Clara Van Karnebeek; Lynne A Wolfe; Zarazuela Zolkipli Cunningham; Shamima Rahman; Patrick F Chinnery Journal: Genet Med Date: 2017-07-27 Impact factor: 8.822